Kotey, E.N.2023-12-072023-12-072021-01http://ugspace.ug.edu.gh:8080/handle/123456789/40847PhD. Molecular Cell Biology Of Infectious Diseases.Seasonal influenza viruses are renowned for recurring annual epidemics worldwide. The Influenza A subtypes H1 and H3 are the most dominant and prevalent in recent outbreaks in humans. As with other infectious diseases, vaccines are an important public health tool. However, influenza viruses continue to evolve evading pre-existing or transient vaccine-induced immunity in addition to antigenic pressures associated with antiviral drugs. For this reason, current seasonal influenza vaccines require annual review. Vaccine (immunogen) design, efficacy, and effectiveness presents a formidable seasonal influenza management issue. Passive immunotherapy has been proposed to offer tremendous protection when appropriately used in the management of influenza, either as a substitute or to complement vaccines. A well-designed immunogen that elicits a strong antibody response towards the conserved domains of the surface Haemagglutinin (HA) protein would be critical to avert virus evolution. A detailed analysis of the highly conserved regions spanning the fusion peptide, cleavage site, and the two heptad repeats for the HA gene in over 1000 and 21,000 H1 and H3 strains, respectively was therefore conducted. Chimeric haemagglutinins (cHAs) of these conserved regions were constructed by alignment with consensus sequences generated from exotic HAs (H5 and H9 for H1-based cHAs; H7 for H3-based cHA). These cHAs were successfully expressed in Drosophila S2 cell lines. Mice were then immunized with these cHAs to determine protection against lethal doses in virus challenges against H1 and H3 seasonal viruses. Serum from seroconverted mice applied in challenge experiments indicated the presence of anti-HA specific antibodies with broadly cross-reactive potential against H5 and H7 viruses for H1 and H3-based cHAs, respectively. This study offers an alternative approach whereby multi-subtype or pan-group immunogens could be utilized for the design and generation of cross-reactive antibodies of potential therapeutic value for influenza in humansenVirusesImmunogenicHaemagglutininsInfluenzaThesis